The ability of phagocytic cells to bind to a foreign cell depends in part on the interaction between a form of the complement protein C3 and cell surface receptors for this protein. Our interests in these processes have been two-fold: 1) to measure the kinetic and equilibrium parameters of interaction between C3 and its several activation fragments with their receptors on human cells and 2) to identify the chemical mechanism by which C3 attaches to a target cell membrane. The activation fragments C3b, C3c, and C3d have been purified from limit proteolytic digests of human C3. C3 and C3b have been radiolabeled and specific binding to human erythrocytes and B lymphocytes measured by direct methods. The binding of either ligand was a saturable reaction with an apparent association constant of 1x10 to the 7th power M-1. Specific antibodies have been prepared to each of these fragments and have been used to develop sensitive radioimmunoassays. We are presently investigating the possiblity that a covalent bond between C3b and the membrane may be formed as a result of transesterification. We have detected a single sulfhydryl group upon either enzymatic conversion of C3 to C3b or treatment of C3 with hydroxylamine or hydrazine. It is our hypothesis that this sulfhydryl group is important to the activation of an acyl group within the C3 protein.